Porous cellulose beads are safer than other synthetic polymers and exhibits low non-specific adsorption property. In addition, though porous cellulose beads are classified as polysaccharide, the mechanical strength thereof is high. Furthermore, porous cellulose beads have a number of hydroxy groups, which can be used for introducing a ligand which interacts with a target substance to be adsorbed. Therefore, porous cellulose beads are used for various adsorbent. Such an adsorbent is exemplified by an adsorbent for various chromatographies and an affinity adsorbent. Specifically, an affinity adsorbent is used as a medical adsorbent and used for purifying an antibody medical drug, since a target substance can be efficiently purified and an unwanted substance concentration can be decreased by using the affinity adsorbent. In particular, an adsorbent which is obtained by immobilizing Protein A as an affinity ligand on a porous support is attracting attention as a therapeutic and medical adsorbent for arthritis, hemophilia and dilated cardiomyopathy (For example, Non-Patent Document 1 and Non-Patent Document 2). In addition, an adsorbent which is obtained by immobilizing Protein A as an affinity ligand on a porous support is also attracting attention as an adsorbent for purifying an antibody medical drug. The adsorbent can specifically adsorb and elute an immunoglobulin (IgG).
A method for producing such porous cellulose beads includes a cumbersome step in many cases as compared to the case of an ordinary synthetic polymer, since it is difficult to dissolve cellulose. As such a method, for example, Patent Document 1 discloses a method in which cellulose is dissolved in a solvent such as a calcium thiocyanate aqueous solution and then cellulose is coagulated. It is however difficult to construct facilities which are used for carrying out the method, since the above solvent is highly corrosive and toxic. In addition, it is well known that the cellulose solution used in the method exhibits a strange behavior and that the porous cellulose beads obtained by the method have considerably large pores (for example, Non-patent Document 3). Therefore, when the porous cellulose beads obtained by the method is used as an adsorbent for an antibody and the like, the adsorbent cannot be expected to show a high adsorptive performance, since the specific surface area of the porous cellulose beads is small. On the other hand, there is a method for producing a porous cellulose support by introducing substituents to improve a solubility of cellulose into hydroxy groups of cellulose, dissolving the cellulose in a general solvent, granulating the cellulose, and then removing the substituents (for example, Patent Document 2). However, the method has complicated steps, and a molecular weight of cellulose is decreased during the steps of introducing and removing the substituents. Therefore, the produced support is inclined not to have sufficient strength required for high speed process or large scale procedure, which is recently needed.
As a solvent which can easily dissolve cellulose, an ionic liquid is attracting attention. Non-Patent Document 4 discloses a method for obtaining cellulose beads by dissolving cellulose in an ionic liquid. However, an ionic liquid is not suited for being used as an auxiliary material in industrial level, since an ionic liquid is considerably expensive. In addition, with respect to the safety of an ionic liquid, there is only a few toxicity data and the like thereof, though an ionic liquid may remain. In addition, when an ionic liquid is used for medical purpose or for producing an adsorbent to purify pharmaceutical compound, it is predictable that confirmation of the safety of an ionic liquid is considerably required since an ionic liquid would remain even in a slight amount.
In addition, for example, Patent Documents 3 and 4 disclose a method for dissolving cellulose into a cool sodium hydroxide aqueous solution only. However, in the method described in Patent Document 3, a mixture of cellulose and a hydrogen bond-cleaving solution is heated at 100 to 350° C. under increased pressure, and then the cellulose in the mixture is dissolved in an alkaline aqueous solution. Such a method is not suitable for an industrial production. The method described in Patent Document 4 requires the steps in which cellulose is dispersed in a strong basic solution and the dispersion is frozen and then the cellulose is dissolved.
Patent Document 5 discloses cellulose which can be dissolved in an alkaline solution. However, the cellulose is microfabricated to be microfiber so that the diameter of the microfiber is not more than 1 μm or not more than 500 nm. Such a microfabrication is not suitable for an industrial production.
More recently, Patent Document 6 discloses a method for producing cellulose beads. The method has a step in which cellulose derived from a microorganism is dissolved to obtain a solution in accordance with the method described in Patent Document 4 and the solution is frozen. However, the step is too cumbersome to be applied to an industrial production.